Breath sampling limitations

There are also practical limitations to the selection and use of biomarkers in human studies. The biomarker should be measurable in a relatively available tissue or fluid for example, urine and breath. Sampling blood is an invasive process and so is more difficult to perform although it is done routinely. However, sampling liver tissues from humans for DNA adducts is much too invasive and would not be performed except at the time of autopsy. In addition, the assays for the marker of interest should not be so expensive that the cost of a study using the marker is prohibitive. Finally, the marker must be validated for its accuracy in quantitatively reflecting either exposure or health outcome. Otherwise, the results of the biomarker assays cannot be interpreted. 

The levels of 1,1,2-trichloroethane were studied in 230 personal air samples, 170 drinking water samples, 66 breath samples and 16 food samples from 9 volunteers in New Jersey and 3 in North Carolina (Wallace et al. 1984). In 99% of the cases, no 1,1,2-trichloroethane or only trace amounts were found in the environment, or in the exhaled breath of the people. Specifically, the personal air concentrations of 1,1,2-trichloroethane were below the detection limit in 151/161 samples, 7 contained trace levels, and the others had a very low median value of 0.35 og/m (0.063 ppb). 

Quantitative information is needed for regulatory enforcement situations, where appropriately collected breath samples are compared to BEIs to assess whether exposure limits have been exceeded. BEIs have been developed after thorough studies of pharmacokinetics for a limited number of occupational contaminants. Exhaled air is used as a surrogate for blood when the relationships between exhaled air, alveolar air and (arterial or mixed venous) blood have been established. 

A perfusion-limited, four compartment model was used to simulate the effect of several confounding factors on the levels of several contaminants in the breath, including PERC. The model, which considered metabolic clearance, consisted of a pulmonary compartment, a vessel-rich group, a group of low-perfused tissues containing muscles and skin, and a group of poorly perfused fatty tissues. The authors predicted that intra-day fluctuations in exposure would have a large effect on breath sampled just after the shift, but that the... 

In the medical area, one study using DART has been applied to human breath. Diagnosis through online breath analysis was fonnd to be difficult due to the dispersion of the breath samples in open air. A confined DART ion source (cDART) was developed and this was tested on fonr standard compounds—ethanol, acetone, 2-hexanone, and limonene— with detection limits approaching 1 ppbv after calibration [188]. 

Since currently may be typically 10 precursor ions per second, a typical k is 10" cm s and the reaction time t is of the order 10" s. Then for at the low value of one product ion per second (a sensible detection limit), tiy in the carrier gas is 10 cm". This is a fractional number density of of that of the helium carrier atoms (usually 10 cm" ). Thus for an air or breath sample introduced into the carrier gas at a relative concentration of 1% of the carrier gas, trace gases at a partial pressure of 10 parts per billion (ppb) can be detected and quantified. Clearly, for large /, greater air sample concentrations, and longer integration times for /p, the sensitivity can be improved and the detection limit lowered. The experimental configuration for this SIFT analytical method is indicated in Figure 8. A transportable version of the SIFT is now available commercially for use in situ for breath and environmental analyses. 

A vital point to note is that the mass spectrum of the product ions in much simpler than would be obtained using electron impact ionization of the air or breath sample, because chemical ionization is used. However, only a limited number of precursor ions can be used, which must not react at a significant rate with the major components of air or breath, N2, O2, CO2, H2O and Ar, but obviously must react efficiently with the trace gases in the sample. In this respect H30% NO+ and O are the prime candidates, and SIFT studies of a great number of the reactions of these three ions with a wide variety of organic and inorganic compounds have shown that H30 and NO+ are of widest application, with being useful for fewer... 

Given all of the problems associated with analytical methods for breath sampling and analysis, it is not surprising that to date the majority of research associated with breath analysis and PTR-MS has been limited to proof-of-principle trials which may not have been using ideal breath sampling procedures. Often these studies have also involved an insufficient number of patients and provided little detailed analysis. In-depth clinical trials to substantiate the effectiveness of VOCs as selective biological indicators of disease are required, but these are expensive and time-consuming. 

This knowledge is also important in order to determine if air tests conducted by OSHA compliance officers are valid. For example, if threshold limit value in the health standard is an 8-hour time-weighted average, the air sample should be obtained by sampling over the entire shift in the employee s breathing zone. It cannot be measured by a few short term samples, even if spaced over the full shift unless the worker is in a relatively fixed location with no variation in his work procedure or in the process. Such an event is generally the exception rather than the rule. 

For occupational measurements of airborne concentrations, NIOSH (1977a) recommended the use of a midget impinger for sampling breathing zone air and the methylene blue/spectrophotometric method for the analysis of hydrogen sulfide. The detection limit was 0.20 g/m3 (0.14 ppb). 

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